Immune-related long noncoding RNA zinc finger protein 710-AS1-201 promotes the metastasis and invasion of gastric cancer cells

Wei Ding, Wei-Wei Chen, Yi-Qin Wang, Xue-Zhong Xu, Yi-Bo Wang, Yong-Min Yan, Yu-Lin Tan
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Abstract

BACKGROUND Gastric cancer (GC) is a prevalent malignant tumor of the gastrointestinal system. ZNF710 is a transcription factor (TF), and zinc finger protein 710 (ZNF710)-AS1-201 is an immune-related long noncoding RNA (lncRNA) that is upregulated in GC cells. AIM To assess the correlation between ZNF710-AS1-201 and immune microenvironment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells. METHODS We obtained data from The Cancer Genome Atlas and Wujin Hospital. We assessed cell growth, migration, invasion, and programmed cell death using cell counting kit-8, EdU, scratch, Transwell, and flow cytometry assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to identify the potential downstream targets of ZNF710-AS1-201. RESULTS In GC tissues with low ZNF710-AS1-201 expression, immunoassays detected significant infiltration of various antitumor immune cells, such as memory CD8 T cells and activated CD4 T cells. In the low-expression group, the half-maximal inhibitory concentrations (IC50s) of 5-fluorouracil, cisplatin, gemcitabine, and trametinib were lower, whereas the IC50s of dasatinib and vorinostat were higher. The malignant degree of GC was higher and the stage was later in the high-expression group. Additionally, patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates. In vitro, the overexpression of ZNF710-AS1-201 greatly enhanced growth, metastasis, and infiltration while suppressing cell death in HGC-27 cells. In contrast, the reduced expression of ZNF710-AS1-201 greatly hindered cell growth, enhanced apoptosis, and suppressed the metastasis and invasion of MKN-45 cells. The expression changes in ZNF710 were significant, but the corresponding changes in isocitrate dehydrogenase-2, Semaphorin 4B, ARHGAP10, RGMB, hsa-miR-93-5p, and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201, as determined by qRT-PCR. CONCLUSION Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells. It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC. Nevertheless, it is still necessary to determine the specific targets of the ZNF710 TF.
免疫相关长非编码 RNA 锌指蛋白 710-AS1-201 促进胃癌细胞的转移和侵袭
背景 胃癌(GC)是一种常见的胃肠道恶性肿瘤。ZNF710是一种转录因子(TF),锌指蛋白710(ZNF710)-AS1-201是一种与免疫相关的长非编码RNA(lncRNA),在胃癌细胞中上调。目的 评估 ZNF710-AS1-201 与免疫微环境特征之间的相关性,并研究 ZNF710-AS1-201 在 GC 细胞侵袭和转移过程中的作用。方法 我们从癌症基因组图谱和武进医院获得了数据。我们使用细胞计数试剂盒-8、EdU、划痕法、Transwell 和流式细胞术等方法评估了细胞的生长、迁移、侵袭和程序性细胞死亡。实时定量聚合酶链反应(qRT-PCR)用于鉴定 ZNF710-AS1-201 的潜在下游靶标。结果 在 ZNF710-AS1-201 低表达的 GC 组织中,免疫测定检测到各种抗肿瘤免疫细胞的显著浸润,如记忆 CD8 T 细胞和活化 CD4 T 细胞。在低表达组中,5-氟尿嘧啶、顺铂、吉西他滨和曲美替尼的半数最大抑制浓度(IC50)较低,而达沙替尼和伏立诺他的IC50较高。高表达组 GC 的恶性程度更高,分期更晚。此外,ZNF710-AS1-201高表达组患者的总生存率和无病生存率均较低。在体外,ZNF710-AS1-201的过表达大大增强了HGC-27细胞的生长、转移和浸润,同时抑制了细胞死亡。相反,减少 ZNF710-AS1-201 的表达则会大大阻碍 MKN-45 细胞的生长、增强其凋亡、抑制其转移和浸润。ZNF710的表达变化显著,但通过qRT-PCR测定,过表达或敲除ZNF710-AS1-201后,异柠檬酸脱氢酶-2、Semaphorin 4B、ARHGAP10、RGMB、hsa-miR-93-5p和ZNF710-AS1-202的相应变化不一致,也没有统计学意义。结论 免疫相关 lncRNA ZNF710-AS1-201 促进了 GC 细胞的转移和侵袭。看来,ZNF710-AS1-201 和 ZNF710 有可能成为治疗 GC 的有效靶点。不过,仍有必要确定 ZNF710 TF 的特定靶点。
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